The research objectives are: 1) to isolate and identify biologically active lipids of virulent tubercle bacilli and to assess their roles in pathogenesis. The mycobacterial sulfatides are lysosomotropic in macrophages and abolish phagolysosome formation. We seek understanding of mechanisms; of how this activity affects intracellular disease and how it can be antagonized. 2) Synthesis studies involve preparations of analogs of cord factor and intermediates to serve as haptenes in protein conjugates. Our studies involve mass cultivation of tubercle bacilli, extraction and purification of individual lipids by chemical and physical methods. Sulfatide activities will be studied in cultured macrophages and in animal experiments.